Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5-TTTC[CG]CGC-3 found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F-4 binds with high affinity to RBL1 and RBL2. In some instances, can also bind RB protein.
Pathway
Adipogenesis; Cell Cycle; Cell Cycle, Mitotic; Cell cycle; Cyclin D associated events in G1;
Citations
Publication ()
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References
Feature extraction via composite scoring and voting in breast cancer
BREAST CANCER RESEARCH AND TREATMENT
Authors: Koch, Martin; Hanl, Markus; Wiese, Michael
Identification and characterization of tumor subtypes using gene expression profiles of triple negative breast cancer patients. Microarray data of four breast cancer studies were pooled and evaluated. Molecular subtype classification was performed using random forest and a novel algorithm for feature extraction via composite scoring and voting. Biological and clinical properties were evaluated via GSEA, functional annotation clustering and clinical endpoint analysis. The subtype signatures are highly predictive for distant metastasis free survival of tamoxifen-treated patients. Consensus clustering and the novel algorithm proposed three triple negative subtypes. One subtype shows low E2F4 gene expression and is predictive for survival of ER negative breast cancer patients. The other two subtypes share commonalities with luminal B tumors. Classification of breast cancer expression profiles may reveal novel tumor subtypes, possessing clinical impact. Furthermore, subtype characterizing gene signatures might hold potential for novel strategies in cancer therapy.
Novel functions for the transcription factor E2F4 in development and disease
The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer. Some of these new functions are independent of the RB family and involve direct activation of target genes. Here we review the canonical functions of E2F4 and discuss recent evidence expanding the role of this transcription factor, with a focus on cell fate decisions in tissue homeostasis and regeneration.
COA
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